Daclizumab versus Antithymocyte Globulin in High-Immunological-Risk Renal Transplant Recipients

Abstract

Nondepleting anti-CD25 monoclonal antibodies (daclizumab) and depleting polyclonal antithymocyte globulin (Thymoglobulin) both prevent acute rejection, but these therapies have not been directly compared in a high-risk, HLA-sensitized renal transplant population. We randomly assigned 227 patients, who were about to receive a kidney graft from a deceased donor, to either Thymoglobulin or daclizumab if they met one of the following risk factors: current panel reactive antibodies (PRA) Ͼ30%; peak PRA Ͼ50%; loss of a first kidney graft from rejection within 2 yr of transplantation; or two or three previous grafts. Maintenance immunosuppression comprised tacrolimus, mycophenolate mofetil, and steroids. Compared with the daclizumab group, patients treated with Thymoglobulin had a lower incidence of both biopsy-proven acute rejection (15.0% versus 27.2%; P ϭ 0.016) and steroid-resistant rejection (2.7% versus 14.9%; P ϭ 0.002) at one year. One-year graft and patient survival rates were similar between the two groups. In a comparison of rejectors and nonrejectors, overall graft survival was significantly higher in the rejection-free group (87.2% versus 75.0%; P ϭ 0.037). In conclusion, among high-immunologicalrisk renal transplant recipients, Thymoglobulin is superior to daclizumab for the prevention of biopsyproven acute rejection, but there is no significant benefit to one-year graft or patient survival.

Polyclonal Antithymocyte Globulin and Cardiovascular Disease in Kidney Transplant Recipients

“…1,2 In such patients, benefits likely overcome the increase in the risk of CVEs. However, in our view, these patients should be considered at very high risk of cardiovascular complications and taken over in this way.…”

“…ATGs have potent immunosuppressive properties and have been proven to be superior to anti-CD25 mAb in immunologic highrisk patients. 1,2 These polyclonal antibodies are a complex mixture of antibodies with multiple specificities directed against both T and non-T cells. 1,2 They produce profound T-cell depletion 1,2 and induce persistent changes in T-cell subsets characterized by a low…”

Effect of Immunosuppressive Drugs on Humoral Allosensitization after Kidney Transplant

“…48 In practice, ATG should be preferred in sensitized patients without DSAs, because two randomized clinical trials showed beneficial short-term effects on acute rejection, graft function, and survival (however, the relationship between induction immunosuppression, dnDSAs, and AMR was not specifically addressed). 49,50 In a more recent trial, Brokhof et al 51 reported in a cohort of 114 moderately sensitized recipients of deceased donor renal transplants that induction with ATG is associated with a reduction in the occurrence of dnDSAs and AMR compared with basiliximab. However, it should be noted that, in this study, (1) the difference became statistically different only at 3 years, (2) only a few patients assigned to basiliximab had a follow-up at 36 months, and (3) the patients who received ATG also received more plasmapheresis and IVIg than the patients who received rituximab.…”

Tailor-Made Induction Therapy in ‘Low Risk’ Renal Transplants; A South Asian Perspective

“…This advantage was also seen among highly sensitized and 'high risk' recipients, making ATG the induction therapy of choice in such patients [36,37]. Therefore, considering the adverse effect profi le of ATG, it is mostly reserved for transplants categorized as 'high risk' of early rejection [5].…”